PROJECT 3: Establishing a Platform for Clinical Improvement for Children with HIV-Associated Malignancies in Sub-Saharan Africa Outcomes for children with cancer in sub-Saharan Africa (SSA) are unacceptably poor, with fewer than 20% of those diagnosed surviving. By contrast, over 85% of children with cancer in the United States survive. The HIV epidemic complicates the landscape of pediatric malignancies in SSA. In SSA, there has been an emphatic association between HIV infection and Kaposi sarcoma (KS), with a 40-fold increase in KS incidence in children in Uganda. And although less pronounced, associations between HIV and mature B cell non-Hodgkin lymphoma (MB-NHL) have been established throughout the region. Not only has HIV impacted the frequency of cancer in SSA, children with HIV have inferior outcomes compared to their HIV-uninfected contemporaries. Over the past fifteen years, there has been a concerted effort to enable treatment of HIV-infected children in SSA with antiretroviral therapy (ART). In partnership with collaborators in SSA, Global HOPE aims to lay the foundation for an international collaborative clinical trial network: Pediatric HIV/AIDS & Infection-Related Malignancies Research Consortium for Sub-Saharan Africa (PARCA). The central problem faced in SSA is the significant burden of HIV-associated malignancies in children and the poor survival of these patients. The overall goal of this project is to establish a standardized multi-site strategy to deliver safe and effective disease-specific and risk-stratified care to children with KS and MB-NHL in SSA. We plan to achieve this goal through the following specific aims: Aim 1: Evaluate current practices and outcomes of children treated for cancer at PARCA sites to identify and address barriers to implementation of standardize treatment regimens. We will perform assessments of current clinical practices in SSA for children with HIV-associated and HIV-negative KS and MB-NHL with focus on risk-stratification, delivery of therapy, and supportive care. Based on these results, we will identify and address gaps in implementation of standardized regimens. Aim 2: Determine the feasibility of implementing standardized treatment regimens for pediatric KS and MB-NHL across PARCA sites. We will test the feasibility of implementing standardized, evidence-based, risk- stratified treatment regimens for HIV-associated and HIV-negative KS and MB-NHL in Uganda and Malawi. Feasibility of this approach will be determined by evaluating accuracy of risk-stratification, completion of prescribed regimen, toxicity, treatment abandonment, and 1-year event-free and overall survival. Aim 3: Investigate clinical and biological characteristics associated with clinical outcomes of children with KS and MB-NHL treated on standardized PARCA treatment regimens. In order to identify clinical and biology factors that may inform future risk-stratification strategies, we will evaluate the clinical significance of baseline staging methods, HIV status, tumor biomarkers and explore potential for plasma cytokines to predict response to therapy.